My thesis work proposes to investigate and examine the effects and applications of organic base solutions possessing high proton affinity values as potential co-matrices for the improvement of MALDI-TOFMS analysis of oligonucleotides. The goal of this work is to provide a simple technique which alleviates the two common problems affecting characterization of Oligonucleotide molecules: cation adduction and poor molecular ion stability. A two- component matrix system was developed in which traditional MALDI matrices for oligonucleotide analysis such as THA, ATT, HPA, are combined with an organic base solution with a high proton affinity such as: triethylamine, piperidine, or imidazole. The role of the MALDI matrix is to promote desorption and ionization of the oligonucleotide, while the organic base assumes the role of a cation scavenger, reducing the presence of adduct peaks in the spectra. Experiments demonstrating the reduction of alkali metal cation adduct formation (RCMS, 1997) and enhanced molecular ion stability (JASMS, 1998) have been completed. Results demonstrate the effectiveness of the organic bases for cation adduct reduction, improved molecular mass measurements, as well as increased molecular ion stability. These two projects have provided the basis for continuing studies focusing on the applications of the organic base co-matrix to high molecular weight samples and phosphorothioate oligonucleotides.